The present invention relates to novel hexaalkylmelamine (HMM) derivatives having anti-tumor and metal chelating properties.
Hexamethylmelamine (HMM) is a well-known anti-cancer agent introduced for clinical trials in the early 1960's. The drug has been found to have significant activity against ovarian cancer and is also active against human pulmonary and renal tumors in mice. The concurrent use of HMM with cyclophosphamide, methotrexate and 5-fluorouracil has been found to be effective against advanced ovarian adenocarcinoma (Young et al., N. Engl. J. Med., Vol. 299, pp. 1261-1266 (1978)).
Hexamethylmelamine, when employed as an anti-cancer agent suffers from several disadvantages. It is generally administered orally but is poorly absorbed. Furthermore, it causes nausea and vomiting, myelosuppression and neurotoxicity.
A more soluble derivative, pentamethylmelamine, which is a major metabolite of HMM is in the early phases of clinical testing (Rutty et al., Biochem. Pharmacol, Vol. 26, pp. 2385-2391 (1977)).
It is an object of the present invention to provide a derivative of HMM and related compounds having anti-tumor properties as well as metal chelating properties which are more water soluble than and not subject to the same disadvantages of HMM.